Obstructive sleep apnea is emerging as an important risk factor for hypertension, heart failure, and ischemic heart disease. The mechanisms linking obstructive sleep apnea to cardiac and vascular disease are poorly understood. Utilizing recent developments in neural circulatory control and in vascular biology, we have acquired exciting preliminary data that promise mechanistic insight into the association between sleep apnea and cardiovascular disease. These data suggest that patients with sleep apnea have: 1) increased sympathetic neural traffic, tachycardia, and marked impairment of heart rate and blood pressure variability; 2) impaired endothelial vasodilator function; 3) dramatic overnight increases in endothelin, with reductions after continuous positive airway pressure (CPAP) therapy. These interesting findings have led us to propose the overall hypothesis that cardiovascular dysfunction in obstructive sleep apnea is mediated by distinct abnormalities in neural and vasoactive mechanisms. We will test the following specific hypotheses: 1) That patients with sleep apnea have impaired neural mechanisms regulating circulatory control. 2) That patients with sleep apnea have impaired endothelial function, and increased production of endothelin. An important and novel strength of these studies is that the integrity of the hypotheses will be tested with careful exclusion of potential confounding variables such as obesity, hypertension, left ventricular dysfunction and impaired glucose tolerance. These studies build on the applicant's previous experience in neural circulatory control, with exploration of additional dimensions such as spectral analysis of cardiovascular function, and endothelial function, in patients with sleep apnea. This proposal should contribute to the understanding and treatment of cardiac and vascular disease in patients with obstructive sleep apnea.
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